ReviewThe Journal of clinical investigation2017
Intravascular hemolysis and the pathophysiology of sickle cell disease.
Review in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 391 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
391 citing papers in PubMed, 3 syntheses or guidelines pooled it, 682 citations in OpenAlex.
- Clinical and Genetic Predictors of Sickle Cell Nephropathy: A Global Systematic Review.Omics : a journal of integrative biology · 2025Pooled it
- Pooled it
- Effects of corticosteroids in patients with sickle cell disease and acute complications: a systematic review and meta-analysis.Haematologica · 2022Pooled it
- The GLOBE Trial: Efficacy and Safety of L-Glutamine Plus Hydroxyurea Versus Hydroxyurea Alone in Sickle Cell Anemia - A Double-Blind, Randomized StudyTurkish journal of haematology : official journal of Turkish Society of Haematology · 2026Trial
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- Arginine Therapy and Cardiopulmonary Hemodynamics in Hospitalized Children with Sickle Cell Anemia: A Prospective, Double-blinded, Randomized Placebo-controlled Clinical Trial.American journal of respiratory and critical care medicine · 2022Trial
- Kidney failure risk equation and early renal risk in adults with sickle cell disease: comparison with KDIGO classification using measured GFR.Renal failure · 2026Article
- Impact of renal iron overload on sickle cell nephropathy in a humanized mouse model.American journal of physiology. Renal physiology · 2026Article
- Identification of Clinical Sub-Phenotypes of Sickle Cell Disease Using Latent Class Analysis.American journal of hematology · 2026Article
- Subphenotypes of Sickle Cell Disease: A Guide to Targeting Treatment?American journal of hematology · 2026Article
- A global survey of blood transfusion practices for patients with sickle cell disease.Transfusion · 2026Article
- The Unfinished Story of Sickle Cell Nephropathy: A Narrative Review of Knowledge Gaps and Research Imperatives.Journal of clinical medicine · 2026Review
- Extracellular Hemoglobin, Hypoxia, and Macrophage-Mediated Pulmonary Vascular Remodeling in Hemolytic Disease.International journal of molecular sciences · 2026Review
- Proximal tubulopathy in adult sickle cell disease: association of alpha-1 microglobulin.Clinics (Sao Paulo, Brazil) · 2026Article
- TTP-Like Syndrome and Subsequent Non-Aneurysmal Subarachnoid Hemorrhage in HbSC Disease: A Case Report.Clinical case reports · 2026Article
- Beyond Pain: A Pilot Study of Neurodegenerative and Mitochondrial Pathway Alterations in Sickle Cell Disease Using Platelet Proteomics.Medical sciences (Basel, Switzerland) · 2026Article
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Antibody-Dependent and Antibody-Independent Hemolysis in Sickle Cell Disease.Antibodies (Basel, Switzerland) · 2026Review
- Thrombocytosis and the generation of platelet-derived microparticles in the pathophysiology of sickle cell disease.British journal of haematology · 2026Review
- Early Hemolysis, Myolysis and Renal Stress Following Pentaspline Pulsed Field Versus Radiofrequency Ablation of Atrial Fibrillation.European journal of clinical investigation · 2026Observational
331 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.